X-ray diffraction methods will be used to elucidate the molecular structures of chemically-different drugs used in the treatment of grand and petit mal epilepsies, in order to establish the stereochemical determinants of biological activity. Studies will also be undertaken on the structure and nature of binding of copper-binding peptides designed to be potentially useful in the treatment of Wilson's disease. Attempts will also be made to crystallize and determine the three-dimensional structures of enkephalines, and to discover possible stereochemical similarities with morphine-type analgesics. The hypothalamic hormone somatostatin will also be studied. We have previously shown that the important anticonvulsants diphenylhydantoin and diazepam, although chemically unrelated, have striking conformational similarities. We have also determined the molecular structures of procyclidine and trihexyphenidyl, drugs with newly demonstrated anticonvulsant action, and shown that they contain these stereochemical features as well. It thus appears that the efficacies of these four agents against grand mal epilepsy are primarily due to the stereochemical components they have in common. Our recent structural determination of ethyl phenacemide, an open-chain (analagous to an opened hydantoin ring) anticonvulsant, has shown these same stereochemical features to be present, adding weighty support to the stereochemical concepts we've postulated for drug action. We shall now study additional active (diphenylsilanediol, a new 2,4-benzodiazepine, and a newly-synthesized phenobarbitol analogue) and inactive (7-methyl-nor-diazepam and a new 1,3-benzodiazepine) agents and compare their structures in detail with the above anticonvulsants in order to correlate biological activity with molecular stereochemistry. Molecular structure studies will also be performed on agents used in the treatment of petit mal epilepsy. The drugs trimethadione and the ethosuximide, two chemically different but equally potent anti-petit mal drugs, will be structurally elucidated and their stereochemical features compared. Methsuximide and phensuximide will also be considered. We shall use the results obtained from these studies to initiate the syntheses of new anticonvulsant drugs, hopefully with more potency and less toxicity than the presently available agents.